TABLE 1.
Selected Publications on MIBG Therapy for Neuroblastoma
| MIBG treatment dose used | Phase | No. of patients | ASCT | Combination | Salient results | Reference |
| Up-front/induction | ||||||
| First of 2 doses: 157–804 MBq (21.7 mCi)/kg; second dose: 113–727 MBq (3–19.6 mCi)/kg | Retrospective | 66 | No | None | Tolerability established in patients with newly diagnosed stage IV disease (n = 66); after 1 and 2 doses: combined grade 3–4 leucopenia in 9% and 25%, respectively, and thrombocytopenia in 11% and 12%, respectively | 89 |
| Single dose after 10 d of chemotherapy: 5.5–7.4 GBq (7.4– 16.6 mCi)/kg (not more than 200 mCi) | Retrospective | 13 | Yes | Prior chemotherapy | Stages III and IV; newly diagnosed; feasible; responses in patients treated with doses of 444 MBq (12 mCi)/kg and higher | 90 |
| 2–5 doses: fixed dose of 7.4 GBq (200 mCi) for dose 1 and 3.7–5.6 GBq (100–150 mCi) for follow-up treatments | Retrospective | 44 (41 evaluable) | No | None | High-risk neuroblastoma; OR in 66%; PR in 63% (26/41); greater thrombocytopenia with higher cumulative doses | 91 |
| Fixed dose: 3.7–7.4 GBq (100–200 mCi) or 174–563 MBq (4.7–15.2 mCi)/kg for dose 1 and 244–529 MBq (6.6– 14.3 mCi)/kg for dose 2 | Retrospective | 21 | Yes | None | Feasible in 66%; RR: 38%; no stem cell support needed; mild thrombocytopenia | 92 |
| Relapsed/refractory | ||||||
| 2 doses (escalation in cohorts); dose 1: 444–777 MBq (12–21 mCi)/kg; dose 2 (based on cumulative body dose): ≤777 MBq (21 mCi)/kg; tandem; red marrow radiation index based | 1 | 21 | Yes | None | Doses given 14 d apart; red marrow dose levels: 4.0, 6.0, and 8.0 Gy; mild toxicity; double MIBG therapy feasible | 36 |
| Single dose of 555–666 MBq (15–18 mCi)/kg | 2 | 19 with neuroblastoma; 2 with metastatic PGL/PHEO | Yes | Arsenic trioxide | Toxicity of combination manageable; objective RR: 29% | 72 |
| Dose escalating from 296 to 666 MBq (8 to 18 mCi)/kg | 1 | 27 | Yes | Vorinostat (escalation of dose from 180 to 270 mg/m2) | High-risk relapsed or refractory neuroblastoma; toxicity of combination manageable; RR: 12% | 74 |
| 555–666 MBq (15–18 mCi)/kg; maximum cumulative dose: 44.4 GBq (1,200 mCi) | 1/2 | 32 | Yes | Irinotecan and vincristine | Advanced high-risk neuroblastoma; toxicity of combination manageable; thrombocytopenia and grade 3 diarrhea common toxicities; RR: 32% | 75 |
| 444–666 MBq (12–18 mCi)/kg | 1 | 24 | Yes | Myeloablative chemotherapy | Refractory neuroblastoma; MTD at 444 MBq (12 mCi)/kg; combination feasible; hepatotoxicity encountered; RR: 27% | 78 |
| 444–666 MBq (12–18 mCi)/kg (no carrier added) | 1 | 9 | Yes | None | 131I-MIBG dosimetry study to assess renal, liver, and lung doses before therapy; toxicities similar to those of conventional MIBG therapy; RR: 27% | 79 |
| 444 MBq (12 mCi)/kg in patients without stem cell treatment (n = 16); 666 MBq (18 mCi)/kg in those with stem cell treatment | 2 | 164 | Yes (33%) | None | Progressive, refractory, or relapsed neuroblastoma; RR: 36% (148 patients treated with 666 MBq [18 mCi]/kg; 16 treated with 444 MBq [12 mCi]/kg); CR + PR: 36%; OS: 49% at 1 y and 29% at 2 y | 80 |
| 1–6 doses: 82–578 MBq (2.2–15.6 mCi)/kg | Retrospective | 47 | No | None | Relapsed, refractory, or metastatic neuroblastoma; RR: 46% | 82 |
| 2.4–12.1 GBq (65–327 mCi), based on WB dosimetry | 1/2 | 25 | No | None | Dosimetry-based approach to delivering 1–2.5 Gy of WB absorbed dose; 80% with grade 3–4 thrombocytopenia at 2.5-Gy WB dose; ORR: 33% | 83 |
| 111–666 MBq/kg (3–18 mCi)/kg | 1 | 30 | Yes, in some | None | High-risk, relapsed neuroblastoma; ASCT required in most patients receiving ≥444 ΜΒq (≥12 mCi)/kg; DLT: 555 MBq (15 mCi)/kg; response in 37%; CR in 1 patient | 85 |
| 2 doses of 666 MBq (18 mCi)/kg (tandem) ∼6 wk (up to 100 d) apart | Retrospective; safety–efficacy 2 | 76 (41 with second treatment) | Yes | None | Extensively pretreated relapsed neuroblastoma; RR to double MIBG therapy: ∼30% | 94 |
| Median dose: 0.44 GBq/kg (11.89 mCi) | Retrospective | 111 | No | Yes | Stage IV neuroblastoma with refractory disease; better event-free 3-y survival in patients who received MIBG therapy; however, MIBG therapy did not improve survival in patients who had refractory neuroblastoma and were undergoing ASCT | 96 |
| 1–5 doses: 1.1–4 GBq (30–108 mCi)/treatment | 2 | 26 | No | None | Stage III–IV refractory, relapsed disease; 8 patients with prior ASCT; palliation of pain in 50%; objective response: 0% | 98 |
| 2 doses; dose 1: 444 MBq (12 mCi)/kg; dose 2 based on remainder for 4-Gy WB dose | Feasibility | 8 | Yes | Topotecan | In vivo dosimetry for 4-Gy WB dose; MIBG doses given 15 d apart; combination feasible; range of measured absorbed WB doses from treatment: 3.7–4.7 Gy | 126 |
RR = response rate; OR = overall response; PR = partial response; DLT = dose-limiting toxicity; CR = complete response; OS = overall survival; WB = whole body; ORR = objective response rate; MTD = maximum tolerated dose.